Advances In Science Could Give Way To Limited NIH Funding
By Trisha Gladd, Editor, Life Science Connect
According to a recent article in Newsweek, academic institutions can be credited with the discovery of more than half of breakthrough drugs in recent decades, such as cancer treatments Gleevac, Herceptin, and Yervoy. Considering how much pharma companies invest in R&D (a recent survey of PhRMA members indicates a R&D spending total in 2015 of $51.2 billion), that fact is pretty overwhelming, albeit not surprising. Biomedical research has always played a critical role in not just drug discovery but also the U.S.’s competitiveness in the global market.
However, funding allocated to the National Institute of Health (NIH) has declined considerably over the last decade, particularly the last five years, despite the fact that the cost of conducting biomedical research has gone up. According to Dr. David Wood, associate professor of chemical and biomolecular engineering at Ohio State University, a major challenge in the industry right now is keeping pipelines full with novel targets and novel therapeutic modalities. Without enough NIH funding, academia will be significantly slowed for making innovative discoveries beyond what he refers to as the “low-hanging fruit.” Discoveries in basic science that have fueled so much of pharma’s pipeline for so long could cease to exist.
“There are a finite number of proteins that the body makes and there are a finite number of targets that those proteins hit,” explains Dr. Wood. “A large majority of human disease-related targets have been identified and molecules that target them have been produced, purified, and put through clinical trials. Many of these targets are receptor molecules for diseases like cancer and rheumatoid arthritis, and many of the therapeutics are human cytokines and antibodies, but again, there are a finite number of disease-related interactions that can be exploited. Once you’ve found antibodies or other molecules that hit those disease-related targets, there’s not much more you can do. Most of the obvious drugs and obvious targets have been identified and exploited, so now you have to go to non-obvious things and those are a lot harder to discover and involve much greater risk. This is where government-funded academic research has traditionally made the greatest impact.”
In May, Dr. Sally Rockey, NIH deputy director for extramural research, delivered a plenary presentation at the NIH Regional Seminar on Program Funding and Grants Administration in Baltimore. In her speech, she discussed the history of NIH funding and the impact it’s had on biomedical research. From 1998 to 2003, the NIH budget doubled. Institutions started to grow as a result, bringing in more students, faculty, and even new construction. Dr. Rockey says this was not done with the notion that the budget would double again but with the thought that after the doubling was over, the NIH budget would get into a predictable trajectory that would allow academia to sustain this growth. That didn’t happen. Budget cuts in 2010 and then sequestration in 2013 decreased funding considerably. Without budget predictability, the NIH is now forced to be very conservative with grants. This is where we could see a significant impact to both the pharmaceutical industry and patients.
The Life Of A Proposal
If a proposal is written to the NIH, it goes through a screening process where it’s determined what “study section” will review it. A typical study section may have 20 to 30 referees who evaluate 50 or more grant proposals, where the referees are drawn from industry and academia based on the match between their expertise and the topic of the study section. Each proposal is scored by the three most qualified referees for that proposal in each study section on a scale of 1 to 9, with nine being the least desirable score. The average of those initial three scores determines the order in which the proposals will be read and discussed by the entire study section. The study section then meets at a centralized location to discuss each of the proposals in the top 50 percent and then everybody votes. Each proposal is again scored on a scale of 1 to 9 and an “overall impact score” is determined. Those proposals that are not in the top 50 percent are not given a score and are recorded as “Not Discussed”. This impact score is turned into a percentile, and those with the highest impact score will generally receive funding. The cutoff percentile, below which a proposal becomes highly unlikely to be funded, is referred to as the “pay line”.
In order to help new professors establish their research programs, the NIH will sometimes relax the pay line for those seeking their first standard grant. When Dr. Wood submitted his first proposal, he qualified for a doubled pay line due to his new investigator status, which at that time, meant he had to qualify in at least the sixteenth percentile (regular investigators had to score above the eighth percentile). When the scores came back though, he found himself at the twentieth percentile, which wasn’t nearly high enough.
Historically, what the NIH refers to as their “success rate” with grant approvals has been at 30 percent. The success rate is defined as the number of awarded grants divided by the total number of applications. In 2013, the success rate for the NIH hit an all-time low of around16 percent, where many study sections were funding at single digit percentile scores. In 2014, it was 18 percent. “We leave so much good science on the table,” says Dr. Rockey. “[Decreased success rates] make distinguishing good science much more difficult because if you’re funding up to the thirtieth percentile, you’re pretty convinced that things above that 30 percent have a different quality of those below it. But if you’re trying to differentiate something that’s in the seventeenth percentile and something that’s in the 15th, I can guarantee you there isn’t much difference between the quality of that science.”
Lost Opportunities
For scientists, this number not only measures their competition but also their chances of qualifying for funding. “It becomes a bit of a crapshoot as to whether or not you’re going to get funding,” she explains. “Because, if our pay lines [percentiles] at an institute are eight percent, you could be in the top percentile and not get funded.” For his proposal, Dr. Wood scored high, specifically in the top fifth of all the proposals to that institute, including those from seasoned investigators. Nonetheless, he knew as soon as he learned of it that he was nowhere near where he needed to be to actually get funded, which can be frustrating and disheartening.
In addition to submitting proposals, he has also been on review panels for NIH proposals and has seen the effects of a limited funding budget. He recalls a proposal for a small business grant where an approach to treating an intractable pediatric brain cancer using a highly unconventional and potentially dangerous method had been discovered. “The data looked very interesting,” explains Dr. Wood. “But in that room, we have to choose: are we going to go with a drug that won’t have as much impact but has a much higher probability of success or are we going to go with a radically new idea that may kill the patient—or may suddenly provide a breakthrough that could save thousands of lives? In the old days, you could say ‘let’s do both,’ but now you can’t.” With a lack of funding, the panel must, as Dr. Rockey put it, leave a lot of great science on the table. “There are numerous well-respected, highly-trained scientists who are writing proposals for interesting ideas to cure diseases, such as cancer, yet in many cases, up to 92 percent of their proposals are being rejected in a given cycle,” says Dr. Wood. “Who can say what the impacts of these funding cuts might be in terms of lost lives and lost economic opportunities?”
In Dr. Rockey’s speech, she told the audience. “This is an unprecedented time for science. Our base knowledge of how things work is bigger than ever before coupled with technological advances, which means there’s amazing opportunity out there and we have to take advantage of those opportunities.” However, until the funding is available, the opportunity to take advantage of a ripening industry could be lost.